ABSTRACTBackground: Only sparse scientific evidence supports the notion that the shortest possible response time relates to improved patient outcomes in acute conditions, other than out-of-hospital cardiac arrest and trauma. Confounders such as bidirectional causality and confounding by indication may influence patient-centered outcomes, which may prevent actionable conclusions from literature reviews. The purpose of the systematic literature review was to assess current evidence on association, if any, between ambulance and helicopter response times and survival in all patient categories treated by ambulance or helicopter services. Methods: The systematic search was conducted in MEDLINE, Cochrane Library, EMBASE, CINAHL, Scopus, and Clinical Trial Registries. No time language or language limitations were imposed to avoid missing relevant literature. All study designs and settings identified as relevant to the topic were eligible. We retrieved data from a predefined template. Two reviewers worked independently, and conflicts were resolved by a third reviewer. The researchers used PRISMA guidelines for abstracting data and GRADE methodology for assessing data quality and validity. Data were pooled using a random-effects model. As per study protocol, the primary study outcome was patient survival, and the main measurement was response time for emergency medical services vehicles. Results: We included 115 studies that in total included 691,056 patients, ranging from 64 til 182,895 patients in the individual studies. The overall median survival rate was 11.5% (IQR 5.2; 25.8). Response time varied between 1.10 and 48.62 minutes. The predefined domains and items of interest were accounted for in 46.7% of the included literature. Certainty of evidence was very low as per GRADE methodology.Conclusions: The main finding of this literature review was indicative of no statistically significant association between ambulance and helicopter response times and patient survival, as the studies addressed the topic very diversely. We found substantive research and knowledge gaps and very low certainty of evidence. Therefore, no actionable conclusions can be made from this systematic review.